Part 28. Neuromuscular Disorders

Part 28 : 메리놀 병원

PART 28. Neuromuscular Disorders

   ; disorders of the motor unit

     specifically excludes suprasegmental disorders, such as cerebral palsy

 

  * motor unit 구성 (4)

      (1) a motor neuron in the brain stem or ventral horn of the spinal cord;         (2) its axon that, together with other axons, forms the peripheral nerve;

      (3) the neuromuscular junction;

      (4) all muscle fibers innervated by a single motor neuron.

   motor unit  suprasegmental or upper motor neuron control 영향을 받음.

   Diseases of the motor unit are common ln children.

 

 ) Many chromosomal loci specific neuromuscular diseases에서 규명

        (  as a result of genetic linkage analysis studies

               and the isolation and cloning of a few specific genes.)

     - Duchenne muscular dystrophy  genetic defect

             ; deletion of nucleotide sequences

             ; defective protein product, dystrophin 동반

     - myotonic muscular dystrophy genetic defect

             ; expansion rather than a deletion in a codon

   * nemaline rod myopathy and limb-girdle muscular dystrophy; AD & AR

       - 다른mendelian genotypes이면 different diseases

            

   * inheritance patterns and chromosomal and mitochondrial loci of common

      neuromuscuiar diseases affecting rotants and children are summarized

                       ( Table 559-1 )                          

Chapter 558. Evaluation And Investigation

Clinical Manifestations

  1.Tone and strength should not be confused:

       - Passive tone is range of motion around a joint;

       - active tone is physiologic resistance to movement.

       - Head lag when an infant is pulled to a sitting position from supine

            ; a sign of weakness, not of low tone.

       - hypotonia may be associated with normal strength or with weakness

 

  2.myopathies follow a Proximal distribution of weakness and muscle wasting

           (with notable exception of myotonic muscular dystrophy)

    neuropathies are generally distal in distribution

           (with the notable exception of juvenile spinal muscular atrophy).

 

  3.Tendon stretch reflexes

       - generally lost in neuropathies and in motor neuron diseases

       - diminished but Preserved in myopathies.

  4.Fasciculations of muscle ( tongue에서 가장 관찰)

       - sign of denervation.

  5.Sensory abnormalities indicate neuropathy.

  6.Fatigable weakness - characteristic of neuromuscular junctional disorders.

  7.Myotonia - specific for a few myopathies.

  8.Muscle pain or myalgias

   ; associated with acute disease of either myopathic or neurogenic origin.

     Muscular dystrophies and SMA - not associated with muscle pain

     Myalgias; in several metabolic diseases of muscle and in ischemic myopathy.

  9.Contractures of muscles - occur in both myopathic and neurogenic diseases.

 10.thorax with congenital NMD;  funnel shape, thin and radiolucent rib

      due  to intercostal  muscle weakness  during intrauterine growth.

     - characteristically in infantile spinal muscular atropy

      but in myotubular myopathy, neonatal myotonic dystrophy, and other

      disorders.  

11.Generalized hypotonia and developmental delay ; most common presenting Sx

Laboratory Findings

  Serum Enzymes.

    ; creatine phosphokinase (CPK or CK); most useful

                   MM for skeletal muscle,

                   MB for cardiac muscle,

                   BB for brain.

     NM disease universal screening test 되지는 못한다.

      왜냐하면 많은 motor unit disease에서 enzyme증가와 동반되지 않기때문이다.   

   그러나 CK characteristically elevated in certain diseases,

              such as Duchenne muscular dystrophy, and the magnitude of increase

              is.'<haracteristic for particular diseases.

Nerve Conduction Velocity (NCV)

Electromyography (EMG}

      EMG is less useful in pediatrics than in adult medicine

      Characteristic patterns distinguish denervation from myopathic

         involvement.

      The specific type of myopathy is not usually definitively diagnosed,

      but certain specialized myopathic conditions, such as myotonia,

        may be demonstrated.

Muscle Biopsy

      most important and specific diagnostic study of muscle.

      neurogenic and myopathic processes

      type of myopathy and specific enzymatic deficiencies

      vastus lateralis (quadriceps femoris) ; most commonly sampled m.

       ( deltoid muscle should be avoided in most cases,

          because it normally has a 60-80% predominance of type ~ fibers,

      so that the distribution patterns of fiber types are difficult

      to recognize.

Nerve Biopsy

      most commonly sampled nerve ; sural nerve

      (pure sensory nerve supplied small area of skin on the lateral surface of

       the foot)

Electrocardiography (ECG)

    Cardiac evaluation - muscular dystrophies and inflammatory and metabolic

                         myopathies에서는 heart침범이 흔하므로 중요하다.

     early cardiomyopathy 무증상의 conduction defects 찾을수 있다.

Serial Pulmonary Function Tests(PFT)

    muscular dystrophies other chronic or progressive diseases

   of the motor unit경우

Chapter 559. Developmental Disorders Of Muscle

Myogenic Regulatory Genes And Genetic Loci Of Inherited Diseases Of Muscle

Table 559-1

# Four Myogenic Regulatory Genes

    ; shares encoding transcription factors of "basic helix-loop-helix" (bHLH) proteins associated with common DNA nucleotide sequences

    1) *myf-5(myogenic factor 5)

           ; earliest bHEH gene to program the differentiation of myoblasts

    2) *myogenin

           ; promotes fusion of myoblasts to form myotubes

    3) *herculin (also known as mrf-4 and myf-6)

    4) *myoD1

# human locus

  ; myf-5 and herculin on chromosome 12

    ; myogenin on chromosome 1

    ; MyoD1 on chromosome 11

559.1 Myotubular Myopathy

; *maturation arrest of fetal muscles during myotubular stage of development at 8-15wks

Fig. 559-1

Pathogenesis

; Persistently high fetal conc of vimentin and desmin in myofibers of infant intermediate filament proteins (serve as cytoskeletal element in fetal myotubes)

  - nuclei and mitochondria sarcolemmal memranes 부착시켜 central positions으로 유지시켰다가  maturation 따라 intracelluilr organ 변화해서 nuclei periphery 이동하고 mitochondria myofibrils사이에 재분포된다. 동시에 vimentin and desmin 감소한다. vimentin term까지 모두 없어지고,desmin 단지 trace amounts로만 남는다.

; Persistent fetal vimentin and desmin in muscle fibers

  - may be the mechanism of "maturational arrest."

Clinical Manifestation

    ; decreased fetal movement in late gestation

    ; at birth

           - thin muscle mass in axial, limb-girdle, and distal muscles

  ; *severe generalized hypotonia & diffuse weakness

  ; ineffective respiratory efforts requiring ventilalory support.

  ; Gavage feeding because of weakness of muscles of suck and deglutitiion

    ; undescend testicles

  ; weak facial muscle

  ; ophalmoplegia - a few cases

  ; high palate

  ; *thin tongue but no fasciculations

    ; DTR- weak or absent

  ; no cardiomyopathy, CNS or other system abnormalities

Laboratory Findings

     1) Serum CK - normal.

     2) EMG - no denervation

              normal or minimal nonspecific myopathic feature in early infancy

     3) Nerve conduction velocity - slow but  usually normal

     4) ECG - normal

     5) chest X-ray - no cardiomegaly, but thin ribs

Diagnosis

    ; muscle biopsy

           - diagnostic at birth, even in premature infants

    - 90% 이상의 muscle fibers 작고, central 위치한 large vesicular nuclei 단열로 배열됨.

           - nuclei사이 공간은 mitochondria 포함한 sarcoplasm으로 채워짐.

    - Histochemical stains for oxidative enzymatic activity and glycogen

           ; central distribution as in fetal myotubes.

       - 그러나 ATPase stains에서는 myofibril cylinders 성숙된 분화를 보임.

    - connective tissue of muscle, spindles, blood vessels, intramuscular nerves, and motor endplates ; mature

       - Ultrastructural features in neonatal myotubular myopathy; mature

       - Vimentin and desmin ; strong immunoreactivity in muscle fibers

Genetics

  ; X-linked recessive

           - *common traits

    ; AD, AR

    ; genetic linkage on the Xq28

Prognosis

       - 수주 수개월내에  severely affected neonates 75%에서 사망

       - 생존자는 progressive course 거치지 않지만  major physical handicaps

          가지며 거의 걸을수 없고  심한 hypotonia 남긴다.

559.2 Congenital Muscle Fiber-Type Disproportion (CMFTD)

    ; isolated "congenital myopathy"형태나

      아래의 다양한 unrelated disorders 동반되어 나타남

          nemaline rod disease

          Krabbe disease (globoid cell leukodystrophy)

          cerebellar hypoplasia

          certain other brain malformations (see later)

          fetal alcohol syndrome

          some glycogenoses

       Lowe syndrome

          rigid spine syndrome

          some cases of myotonic muscular dystrophy.

Pathogenesis

      gestation 20-28 사이에 muscle histochemical 분화 단계동안 motor unit

      발생에 있어서 abnormal suprasegmental influence때문으로 추정.   

Clinical Manifestations

     1) generalized hypotonia and weakness,

     2) weakness - usually not severe

        respiratory distress and dysphagia - rare

     3) Poor head control and developmental delay for gross motor

        waling 대개 18 - 24 개월까지 연기되나 결국 걸을 수는 있다.

     4) dolichocephalic head and facial weakness

     5) high-arched palate

     6) trunk and extremities - thin, wasted appearance

     7) no myalgias

     8) clinical course - benign and nonprogressive.

Laboratory Findings

      Serum  CK,  ECG, EMG,NCV -  a11 normal in simple CMFTD

Diagnosis

     muscle biopsy ; histochemical fiber types size ratio 불균형.

               type I fibers          type II fibers

                  small              hypertrophic

               type 1 fibers ; more numerous than  type II

Genetics

     대부분의 simple CMFTD  sporadic

     AR ; often  /  AD ; a few

Treatment

     1) No drug therapy is available

     2) Physiotherapy   Mild congeni-

     3) gentle range of motion exercises in mild congenital contracture

     4) rarely plaster casting or surgery.

559.3  Nemaline Rod Myopathy

  1. 정의

   ; Nemaline rod muscle fiber내에  rod-shaped inclusion-like abnormal

      structures로써 foreign inclusion bodies라기보다는 excessive Z-band

      material이다.(그림 559-2)

      화학적으로 rods 주로 alpha-actinin이다.

   ; unusual reaction of muscle fibers to injury라고 생각하기도함,

      ( rod structures 흔치않게 여러diseases에서 발견되므로)

Clinical Manifestations

    infantile form

     1) Generalized hypotonia, weakness including bulbar-innervated

       and respiratory m.

     2) very thin muscle mass

     3) dolichocephalic head, high arched or cleft palate

     4) jaw m. 너무 약해서 입을 다물 없다 (Fig. 559-4).

     5) severely weak at birth,  die in the neonaIal period.

        Survivors - electric wheelchair생활하고,일반적으로 중력을 이기지 못함.

     6) proximal and distal muscles모두 involved

     7) Gastrostomy  for chronic dysphagia.

 

    juvenile form

     1) ambulatory and able to perform most tasks of daily living.

     2) generalized hypotonia, bulbar & resp m.weakness

        - usually not progressive

   * cardiomyopathy ; an uncommon complication.

Laboratory Findings

     1) Serum CK - normal

     2) muscle biopsy - fiber type I predominance + the nemaline rods

Genetic Aspects

     AD, AR

     X-linked dominant- girls

   > AD ;  1q21-23 locus abnormal gene

559.4  Central Core Disease

;AD

; *abnormal gene on chromosome 19q13.1 locus

pathology

    ; central core within muscle fibers

           - amorphous granular cytoplasm without myofibrils & organelles

    ; no enzymatic activities

Clinical Manifestation

    ; infantile hypotonia, proximal weakness, muscle wasting, involvement of facial muscles and neck flexors

    ; nonprogressive & not severely disabling

    ; Congenital dislocated hips, skeletal deformities

         - Scoliosis occurs even without much axial weakness.

    ; malignant hyperthermia 흔히 동반

    ; *serum CK is normal (malignanl hyperthermia crisis때는 제외)

559.5  Brain Malformations And  Muscle Development

 

  1. cerebeilar hypoplasia 갖는 infant  hypotonic하고 

     developmental delay가짐.

  2. Muscle biopsy

     1) delayed maturation of muscle

     2) fiber type predominance

     3) CMFTD

  3. supratentorial lesion brain stem or cerebellar lesion보다

     muscle development 변경시킴

  4. bulbospinal pathway abnormal descending impulse

      differentiation of muscle 결정함.

559.6  Amyoplasia

  -  Congenital absence of individual muscles ; common and  often asymmetric

  -  One of the most common ; the palmaris longus muscle of the ventral forearm

  -  Unilateral absence of a SCM ; one cause of congenital torticollis

  -  Absence of one pectoralis major muscle ; part of the Poland anomalad

  -  severe cases of myelomeningocele에서 lower limb innervation발생되지 않으면

       ; muscles 발생되지 않는다.

  -  sacral agenesis ; mesodermal plate muscle 형성 실패

  -  Absence of one long bone, such as the radius ;

          aplasia or hypoplasia of  carpi flexor radialis 동반

>-  Generalized amyoplasia due to defective myogenic regulatory genes

      ; result in spontaneous fetal loss

      End-stage neurogenic atrophy of muscle is sometimes called amyoplasia,

           but this usage is semantically incorrect.

559.7  Muscular Dysgenesis 

>

 

  1.정의

     ;ectodermal and mesodermal tissues 포함하는 cellular growth 장애

  2.원인

     ;unknown , not a mendelian trait

  3.임상 소견

     1) asymmetric overgrowth of the extremities

     2) verrucous cutaneous lesions

     3) angiomas of various types

     4) thickening of bones

     5) hemimegalencephaly

     6) excessive growth of muscles without weakness

  4.조직 소견

     ; unique muscular dysgenesis

      - Abnormal zones adjacent to zones of normal muscle formation

  * 병인에 있어서  abnormal paracrine growth factors 관여한다고 생각.

559.8  Benign Congenital Hypotonia

  1.정의; nonprogressive hypotonia of unknown origin

  2.임상 소견

     1) 소수에서 slowly acquied gross motor skills 갖기도 하지만,

           weakness or developmental delay 동반되지 않음.

     2) Tendon stretch reflexes - normal or hypoactive

     3) no cranial nerve abnormalities

     4) Intelligence - normal.

  3.진단

     ; muscle biopsy and brain imaging 정상으로 나온후 실시.

  4.예후; good

    contracture 없지만 hypotonia adult까지 지속될 있다.

  5.치료;no specific

  6.complication

     1) recurrent dislocation of joints, especially shoulders

     2) stretch injury, compression, or vascular compromise of

                   nerve roots or of the spinal cord.

        (특히 체조나 circus하는 사람에서 위험성 동반)

559.9  Arthrogryposis

  1. Arthrogryposis multiplex congenita

     ; multiple congenital contractures.

       etiologies encompass both neurogenic and primary myopatbic diseases

       not due to neuromuscular disease

  2. 원인

     1) Myopathies

       ; minor congenital contractures extensive arthrogryposis 빈도가 높다.

        -  myotonic muscular dystrophy

        -  many congenital myopathies

        -  intrauterine viral myositis

     2) Neurogenic

        - infantile spinal muscular atrophy

        - Pena-Shokeir syndrome

        - Marden-Walker syndromes

Chapter 560. Muscular Dystrophies

 

# 4 Criteria Of Muscular Dystrophies

    1) primary myopathy

  2) genetic basis for the disorder

  3) progressive course

  4) degeneration and death of muscle fibers

# Muscular Dystrophy에서 제외되는 질환

  1) neurogenic disease : spinal muscular atrophy

  2) nonhereditary myopathies : dermatomyositis

  3) nonprogressive and non-necrotizing congenital myopathies : CMFTD

    4) nonprogressive inherited metabolic myopathies

560.1  Duchenne And Becker Muscular Dystrophies

# Duchenne MD

    ; *common hereditary neuromuscular disease

  ; incidence

           - 1 : 3,600 liveborn male infants

    ; X-linked recessive trait

  ; *abnormal gene on the X-chromosome at the Xp21 locus

    ; Characteristic Clinical Features

        1) hypertrophy of the calves

        2) progressive weakness

        3) intellectual impairment

        4) proliferation of connective tissue in muscle

# Becker muscular dystrophy

  ; same fundamental disease as Duchenne dystrophy

  ; genetic defect at the same locus

  ; but clinically follows a milder and more protracted course

Pathogenesis

한글판 ♣그림 18-14 (p786)

Clinical Manifestation

# *rarely symptom at birth or in infancy

    ; poor head control

    ; mild hypotonia

    ; appropricate or delayed early gross motor skills(rolling over, sitting, and standing)

Walking 종종  정상적으로 12 mo 이루어지나, hip girdle weakness

   2세경에 나타나 보상적으로 lordotic posture 취한다.

# Gowers' sign

    ; 3 그후 5 - 6세에 나타남

  pseudohypertrophic muscular dystrophy 환아에서, pelvic girdle muscle

  weakness 인해 누워있는 자세에서 일어날 , 몸을 돌려서 엎드린 다음

  손으로 상체를 받히고 무릎을 꿇고 좌우 손으로 차례차례 다리를 잡고

   몸을 일으켜서 일어나   모양.

  완전 기립시는 심한 lordosis보임. 

# Trendelenburg gait (or hip waddle)

 ambulation기간은 다양해서 orthotic bracing, PT, Achilles' tendon

   lengthening으로

  12세까지도 걸을 있음.

  Ambulation  psychological depression scoliosis 예방할 있다.

 distal muscles 기능은 보존되어 pencil, computer keyboard사용 가능

 Respiratory muscle involvement

  - a weak and ineffective cough

    frequent pulmonary infections

    decreasing respiratory reserve

 Pharyngeal weakness

  -> aspiration, nasal regurgitation of liquids, airy or nasal voice

     quality

 extraocular muscles기능 유지

 Incontinence due to anal and urethral sphincter weakness

  -  uncommon and very late event.

 ankles, knees, hips, and elbows contracture

 Scoliosis - common

              also uncomfortable or painful at times.

 enlargement of calves(psedohypertrophy)

     원인> a.infiltration of  muscle by fat

           b.hypertrophy of somr muscle fiber

           c.proliferation of collagen

 calves다음으로 tongue  muscular hypertrophy 생김.(다음순서; forearm)

                          - no fasciculaticms of the tongue

  thigh muscle weakness

Cardiomyopathy -  constant feature

Intellectual impairment - all patients에서 나타나나, 20-30%에서는 IQ70이하

Death

  ; occurs usually at about 18 yr of age

  ; causes of death

       a. respiratory failure in sleep

       b. intractable congestive heart failure

       c. pneumonia

       d. aspiration and airway obstruction.

    Becket muscular dystrophy

    1) boys remain ambulatory until late adolescence or early adult life

    2) DMD 유사하게

       Calf pseudohypertrophy,cardiomyopathy, and elevated serum CK소견

       보이나, Learning disabilities  less frequent

    3) weakness  Becker에서 늦게 나타난다.

    4) Death 20 중반이나 후반, 반이상은  40세까지 생존 가능.

Laboratory Finding

1) serum CK ; 15,000-35,000 IU/L (normal < 160 IU/L)

     2) aldolase and AST ;  increase but are less specific.

     3) Cardiac assessment by EKG and  chest roentgenogram ; essential

     4) EMG ; characteristic myopathic features but  not specific

Diagnosis

            1) muscle biopsy 

         --- in vastus lateralis(quadriceps femoris), gastrocnemius

         ; diagnostic and shows characteristic changes (Figs. 560-1 and 560-2)

         -  Myopathic change

       (1) endomysial connective tissue proliferation

           (2) scattered degenerating and regenerating myofibers

           (3) foci o[ mononuclear inflammatory cell infiltrates

                                  as reaction to muscle fiber necrosis

     2) family history

     3) typical clinical features of Duchenne muscular dystrophy

     4) high concentrations of serum CK

 

   ** >

      specific molecular genetic Dx - confirmation

         ; deficient or defective dystrophin

         by (1) immunohistochemical staining of sections of muscle biopsy tissue

            (2) DNA analysis from peripheral blood

Genetic Etiology And Pathogenesis

     1) 대부분 X-linked recessive이지만,  30% new mutations으로 mother

        carrier아님.

     2) Turner syndrome에서 Xp21 gene deletion갖는 경우 있음

     3) asymptomatic carrier state

                - 80%에서 serum CK 증가; 8-12세때 최고.

                  20%에서    "     정상

     4) carrier state selection

             (1) CK 

             (2) Muscle biopsy

          >(3) specific genetic diagnosis using PCR on peripheral blood ;

                   definitive.

             (4) molecular genetics ; Xp21 site of Duchenne gene 

                 from translocation

 

 > 5) Dystrophin

        (1) 개요 

           - 427 KD cytoskeletal protein

           - encoded by large gene at the Xp21.2 locus

           - subsarcolemmal protein으로서 myofibril A band M band 덮는

              sarcolemmal membrane 부착함.

           - 4개의 distinct region or domain으로 구성

         +- N-terminus; 250 aminoacids 포함하며,

         |              alpha-actinin N-actin binding site 관련이 있음

         +- second domain; largest하며,2800 aminoacids 포함하고,특징적인 rod

         |                 shape가짐

         +- third cysteine-rich domain; alpha-actinin C-terminus 관련이 있음

         +- final C-terminus domain; 400 aminoacids 포함,

               dystrophin chromosome 6 의해 encoded dystrophin related

               protein 독특하다.

          - dystrophin mRNA cardiac and smooth muscle이나 skeletal muscle

             and brain 에서 detection된다. 

       (2) various type of molecular defect in dystrophinopathies

           +- intragenic deletion ; 65% of pt

           +- duplication ; 7%

           +- point mutation of nucleotides 

       (3) clinical spectrum

            - classic Duchenne and Becker MD 뿐만아니라 severe neonatal MD에서

              serum CK 지속적으로 1000 IU/L이사인 무증상의 소아까지 포함

           -  alteration of translation of mRNA

               -> unstable, truncated dystrophin molecule & severe, classical

                  Duchenne dystrophy

              quadriceps myopathy ; milder form of adult onset.

                                    due to abnormal dystrophin molecule

       (4) absence of dystrophin

              --> secondary reduction in several dystrophin-associated

                    glycoprotein in the sarcolemma

              --> loss of linkage to extracellular matrix &

                  sarcolemma susceptible to necrosis

 

       (5) Analysis of dystrophin protein

           +- muscle biopsy

           +- Western blot analysis

           +- tissue section by immunohistochemical methods  using either

           |         fluoscence or light microscopy of antidustrophin antisera              +-lengthy Southern blot process of DNA analysis or more rapid PCR

     * prenatal diagnosis

         ; possible as early as 12 wk gestation

            by sampling chorionic villi for DNA analysis by Southern blot or PCR 

              ; confirm in abortus with Duchenne dystrophy

                      by immunohistochemistry for dystrophin in muscle

Treatment

     1) no medical cure & no method of slowing its progression

     2) cardiac decompenasation --> digoxin

     3) pulmonary infection --> 즉시 치료

     4) immunization for influenza virus and routine vaccination

     5)   good nutritional state유지가 중요

            - not a vitamin deficiencv disease.

                --> excessive doses of vitamins should be avoided

            - calcium intake is important to minimize osteoporosis

            - fluoride supplements

     6) physiotherapy

            ; contracture delay시킴

            - contracture 기능적으로 재활에 이용할 있다

            - exercise 침범된 근육을 강화시키지 못함.

    7) 실험적 단계

      - myoblast transfer therapy

     ;유전적으로 유사한 아버지의 근육에서 얻은 정상 myoblast dystrophic muscle

        주사.

            ; 근육으로 recombinant dystrophin gene 주사

     8) prednisone or other steroid

          ; ontogenesis동안 myotubule apoptosis programmed cell death rate

            감소시킴.

560.2  Emery-Dreifuss Muscular Dystrophy

  1.개요

      - scapuloperoneal or scapulohumeral muscular dvstrophy 알려져 있음.

      - X-linked recessive dystrophy, but no isolated gene

   >- locus ;  on the long arm, within the large Xq28 gene

              다른 질환)  myotubular myopathy

                          neonatal adrenoleukodystrophy

                          Bloch-Sulzberger type of incontinentia pigmenti

     cf. Duchenne muscular dystrophy gene; on the short arm of the X chromosome.

 2. Clinical manifestations

  1) slow progression ;  middle childhood 시작, late adult life까지 생존

  2) 초기에 Contractures of elbows and ankles  scapulohumeroperoneal weakness

  3) No Facial weakness

     No muscle hypertrophy

     No Myotonia

  4) Normal Intellectual function

  5) severe cardiomyopathy ; 때로 사인이 되기도 .

 3. Lab.

     1) serum CK ; only mildly elevated

         ( other X-linked recessive muscular dystrophies 구별시킴)

     2) m biopsy

                - Nonspecific myofiber necrosis

                - endomysial fibrosis

  4. Treatment ;    supportive.

560.3  Myotonic Muscular Dystrophy

(=Steinert disease)

; second most common muscular dystrophy in North America, Europe, and Australia

; incidence - 1:30,000 general population

; *autosomal dominant trait

; *both involvements of striated muscle & smooth muscles of alimentary tract, uterus

; *altered cardiac function

; *endocrinopathies, immunologic deficiency, cataracts, dysmorphic facies, intellectual impairments, other neurologic abnormalities

Clinical Manifestation

    ; almost normal at birth

           - maybe facial wasting or hypotonia

  ; characteristic facial appearance

       - inverted V-shaped upper lip

    - thin cheeks

    - scalloped, concave temporalis muscles

    - narrow head

           - high arched palate due to weak temporal and pterygoid muscles in late fetal life

    ; progressive wasting of distal muscles

        - intrinsic muscles of the hands, dorsal forearm muscles, anterior compartment muscles of the lower legs

           - proximal muscles 결국 atrophy초래 --> scapular winging

    ; tongue - thin and atrophic

  ; long, thin, cylindrical neck due to wasting of the SCM

    ; Gower sign - progressive.

  ; Tendon stretch reflexes - usually preserved.

    ; muscular atrophy and weakness

           - progression into adulthood

    ; Myotonia

        - infancy때는 없고,5세까지는 clinical, EEG 나타나지 않음.

        - 정의 ; very slow relaxation of muscle after contraction

        - demonstrated by

            a. asking the patien! to make tight fists

               and then to quickly open the hands

            b. striking the thenar eminence with a rubber percussion hammer

            c. watching the involuntary drawing of the thumb across the palm

            d. tongue by pressing edge of a wooden tongue blade

               against its dorsal surface and by observing a deep furrow

               that disappears slowly.

           -  myotonia degree of weakness 반드시 비례하지는 않는다.

           Myotonia painful musscIe spasm 아니다.

           myotonic dystrophy에서는 myalgia 없다.

    ; speech - poorly articulated and slurred

        Difficulties with swallowing --> Aspiration pneumonia

        Incomplete external ophthalmoplegia from extraocular muscle weakness.

     8) Smooth muscle involvement of the gastrointestinal tract

        -  slow gastric emptying

        -  poor peristalsis

        -  constipation

        - encopresis ass with anal sphincter weakness

     9) Women ; ineffective or abnormal uterine coreractions during labor

                and delivery

  ; Cardiac involvement

       - heart block in the Purkinje conduction system & arrhythmias

       ---  cardiomyopathy (-)

                   ( unlike most other muscular dystrophies )

    ; Endocrine abnormalities

       - hypothyroidism - common

    - hyperthyroidism - rare

           - Adrenocortical insufficiency ( Addison's crisis )

    - Diabetes mellitus - common

             ( 주로 insulin release disorder )

       - puberty - precocious or delayed

    - Tesiicular atrophy and testosterone deficiency - common in adults

  ; immunologic deficiencies - common ;  low plasma IgG

    ; Cataracts -  congenital

                     childhood or adult life 어느때라도 나타남.

    ; 반수에서 지능 장애가 오나  severe mental retardation 흔하지 않음.

  ; Severe neonatal form of myotonic dystrophy

    - Clubfoot deformity

    - congenital contractures of multiple joints

    - generalized hypotonia,  weakness ; at birth

    - respiratory muscle weakness or apnea

    - distended abd due to  poor peristalsis

    - 1 내에 severely affected neonate 75%에서 사망.

Laborotory Findings

     1) classic myotonic EMG ; infancy때는 나타나지않고

                               toddler  early school years 나타남.

     2) serum CK ; normal or mildly elevated ( 100 단위, never the thousands).

     3) ECG ; annually in earl childhood

     4) ultrasonic imaging of abdomen-to determine diaphragmatic function

     5) chest and abd X-ray, contrast studies of GI motility

     6) Thyroid, adrenocortical function,  carbohydrate metabolism study

     7)Immunoglobulins 검사

Diagnosis

     ;  muscle biopsy

     1) muscle fibers with central nuclei

     2) selective atrophy of histochemical type I fibers

     3) young children -  normal, at least no myofiber necroses

     4) severe neonatal form - maturational arrest

     ---- 대개 불필요

     ---- severe neonatal form에서는 진단적 가치와 함께 예후결정에 도움이 된다.

Genetics

     - genetic detect ; on chromosome 19 at the 19q13 locus

     - deletion이라기보다는 expansion of the gene이며,수많은 반복된 CTG

        ( Cytosine-thyamine-guanine) codon 가짐.

Treatment

       - no specific medical therapy

     1) Physiotherapy and orthopedic treatment of contracture

     2) muscle membrane depolarization threshold상승시키는 drug

          (1) phenytoin ; 40 - 80 umol/L   ---+

          (2) carbamazepine ; 35 - 50 umol/L -+  serum level 유지

          (3) procainamide

          (4) quinidine sulfate         

Other Myotonic Syndromes

Myotonic Chondrodystrophy (Schwartz-Jampel Disease)

    1) 특징

      - generalized muscular hypertrophy and weakness

      - dysmorpic phenotypical feature

         long bone X-ray  Morquio disease 유사

          ... no abnormal mucopulysaccharides

        - Dwarfism

        - joint abnormalities

        - blepharophimosis

     2) AR inheritance.

     3) EMG ; continuous electrical activity in muscle fibers

            ..... myotonia 유사

     4) Muscle biopsy ; nonspecific myopathic feature

                  -  dilated sarcotubular system

Myotonia Congenita ( Thomsen Disease)

     1)특징

        -  generalized muscular hypertrophy, but the large muscles are weak

        - prominent myotonia

     2) onset ; 2 - 3 세경

     3) Dx

        - muscle biopsy ; minimal pathologic changes

        -EMG ; myotonia소견

Paramyotonia

      ;  temperature-related myotonia

          - aggravated by cold

          -alleviated by warm external temperatures

      ; defect in a gene at the 17q l3.1-13.3 locus,

            the identical locus identified in hyperkalemic periodic paralysis.

560.4  Limb-Girdle Muscular Dystrophy

  1. 특징

     1) progressive hereditary myopathies ( hip and shoulder girdle

        주로 affect하나 결국은 distal muscles  atrophic and weak해짐.)

     2) Hvpertrophy of the calves and ankle comractures

           --- potential confusion with Becker's MD

 

 2. 임상상

     1) middle or late childhood이전에는 rare

     2) Low back pain ; presenting complaint

     3) weakness of neck flexors and extensors ; universal

     4) facial, lingual, and other bulbar-innervated muscles ; rarely  involved

     5) progressive weakness and muscle wasting

     6) diminished DTR

     7) cardiac involve; unusual

     8)Intellectual function ; generally normal

  3. DDx

     1) juvenile spinal muscular atrophy (Kugelberg-Welander disease)

     2) myasthenia gravis

     3) metabolic myopathies.

  4.Genetics

      ;Most cases - autosomal recessive inheritance,

       but some AD trait---  benign course with little functional impairment

  5.Dx

     1) EMG and muscle biopsy ; confirmatory evidence of muscular dystrophy

     2) Increased serum CK is usual

     3) ECG ; usually unaltered.

  > autosomal dominant form of LGMD

             - genetic defect위치; the long arm of chromosome 5.

      autosomal recessive disease

                                 ; the long arm of chronmsome 15.

560.5  Facioscapulohumeral Muscular Dystrophy

            ; = Landouzy-Dejerine disease

     -  AD

     -  genetic defect in AD FSH MD ; at  4q35 Iocus

Clinical Manifestation

    ;  earliest and most severe weakness in facial and shoulder girdle muscles

    1) facial weakness

            ( myotonic dystrophy와는 다름 )

         (1) inverted V-shaped upper lip이라기보다는 round하고,

               위아래입술을 내밀고있기 때문에 입이 주름져 보인다. 

         (2) 잠잘때 눈을 감지 못함.

            (<--common expression of upper facial weakness)

         (3) 일부에서  EOM weakness ( ophthalmoplegia - rarely complete)

         (4) 드물게 Mobius syndrome 동반

 2) Pharyngeal and tongue weakness - may be absent

                               never as severe as the facial involvement

 > 3) Hearing loss and retinal vasculopathy동반

          - 특히  early childhood onset 경우에

     4) Scapular winging ; prominent

         (1) Flattening or even concavity of the deltoid contour

         (2) wasted, weak  biceps and triceps brachii muscles

     5) hip girdle and thigh muscle

         (1) strength잃고 atrophy초래

         (2) Gower sign and  Trendelenburg gait

    *  Contractures ; rare

     6) finger, wrist weakness 증상으로 나타나기도 .

     7) weakness of the anterior tibial and peroneal muscles --> foot drop

     8) Lumbar lordosis and kyphoscoliosis

     9) No Calf hypertrophy

 * 대부분MD symmetric weakness이지만, 질환의 경우 asymmetry of weakness

      흔하다.

Laboratory Findings

     1) Serum CK and other enzymes - various

     2) ECG

     3) EMG - nonspecific myopathic muscle potentials.

Diagnosis And Differential Diagnosis

   * muscle biopsy

     (1) extensive proliferation of connective tissue between muscle fibers

     (2) extreme variation in fiber size - hypertrophic and  atrophic myofibers

     (3) scattered degenerating and regenerating fibers

     (4) extensive lymphocytic infiltrates withinn muscle fascicles

  # 2 이하 infant m biopsy mononuclear cell inflammation 있으면

     FSH dystrophy.

  * polymyositis와의 차이점

     (1)  no evidence of autoimmune disease

     (2) steroids and immunosuppressive drugs  clinical course 호전되지 않음

   

  4.TREATMENT

     1) Physiotherapy ; no value

     2) orthopedic measures ; foot drop & scoliosis dffective

     3) reconstructive surgery ; for facial m expression

560.6  Congenital Muscular Dystrophy

; Autosomal recessive inheritance

Clinical Manifestations

    ; *often contractures or arthrogryposis at birth

    ; *diffusely hypotonic

    ; thin muscle mass in the trunk and extremities

    ; poor Head control

    ; Facial muscles - mildly involved

    ; ophthalmoplegia, pharyngeal weakness(+)

  ; weak suck  - not common.

    ; Tendon stretch reflexes - hypoactive or absent

# Walker-Warburg syndrome?

# muscle-eye-brain disease of Santavuori ?

# Fukuyama type

  ; 2nd common muscular dystrophy in Japan (following Duchenne dystrophy)

    ; severe cardiomyopathy

    ; brain malformations

    ; 동반 소견

        - cardiomegaly

        - congestive failure

         - mental retardation

        - seizures

        - microcephaly

         - failure to thrive

    ; *genetic defect at the 8q31-33 locus in Japanese patients

# Other types

    ; Mental and neurologic status ;  most variable

  ; cerebral malformations

             i) severe dysplasias - holoprosencephaly or lissencephaly

            ii) milder conditions - agenesis of the corpus callosum

                                  - focal heterotopia of the cerebral cortex

                                     and subcortical white matter

                                  - cerebellar hypoplasia

Laboratory Findings

     1) Serum CK ; moderately elevated(수백 - 수천 IU/L)

     2) EMG ; nonspecific myopathic features

     3) cardiac assessment

     4) imaging study of the brain.

Diagnosis

     * muscle biopsy - diagnostic

     1) extensive proliferation of endomysial collagen envelops individual

         muscle fibers

     2) perimysial connective tissue and fat ; 증가

     3) disrupted fascicular organization by  fibrosis

Chapter 561. Endocrine Myopathies

 

Thyroid Myopathies

Thyrotoxicosis

  ; proxirnal weakness and wasting

    ; myopathic EMG changes

  ; *induce myasthenia gravis & hypokalemic periodic paralysis

Hypothyroidism

  ; hypotonia, proximal distribution weakness

    ; Kocher-Debre-Semelaigne Syndrome

       - *hypertrophy of weak muscles

           - cretinism 형태임    

  ; serum CK

           - elevated in hypothyroid myopathy and return to normal after thyroid replacement therapy

    ; muscle biopsy

           - myopathic changes

    - myofiber necrosis and central cores.

Hyperparathyroidism

    * 증상   

          1) weakness

          2) fatigability

          3) muscle wasting

    *  parathyroid adenoma제거후에 reversible

Steroid-Induced Myopathy

  1. Cushing disease and iatrogenic Cushing syndrome

      from exogenous corticosteroid adm.

        1) 특징    

              (1)  progressive proximal weakness

              (2) increased serum CK

              (3) myopathic EMG and muscle biopsy

        2) Myosin filaments may be selectively lost.

        3) Fluorinated steroids ( such as dexamethasone)경우 생김

  2. Hyperaldosteronism (Conn syndrome)

        1) episodic and reversible weakness

        2) chronic cases에서는 irreversible proximal myopathy

        3) Elevated CK and even myoglobinuria

                  ; acute attacks중에 때로 발생

Chapter 562. Metabolic Myopathies

562.1  Potassium - Related Periodic Paralysis

 - with transient alterations in serum K (hypokalemia, hyperkalemia)

 - autosomal dominant ; defective gene - 17q13.1-13.3 locus

  1. precipitating conditions

     1) hyperaldosteronism

     2) hyperthyroidism

     3) amphotericin B

     4) ingestion of licorice

  2. Cl/M

     1) periodic paralysis

        : awakening 움직일수 없다가 수분,수시간내에 m. strength 회복

     2) Muscles that remain active in sleep(cardiac m.&diaphragm)-  not affected

     3) attack사이에는 normal

     4) in adult life - attacks 잦아지면서 attack사이에도 permanent weakness

        동반한 progressive myopathy초래

  3. Dx

     1) serum K level 변화 c T-wave changes in the ECG - acute episode동안

     2) CK - mildly elevated(may be)

     3) m. biopsy - attack사이에는 종종 normal

                  - during attack; vacuolar myopathy

     4) hypoglycemia(-) 

562.2  Malignant Hyperthermia

; autosomal dominant(usually)

; *occurs in all patients with central core disease

    - 다른 질환에서 발생할 수도 있다.

; all ages

; c-sec위해 general anesthesia 산모에서 태어난 premature infant 가능

Precipitating Factors

     1) exposure to general anesthetics

     2) even to local anesthetic drugs

Clinical Manifestation

     1) sudden extreme fever

     2) rigidity of m.

     3) metabolic & respiratory acidosis

     4) serum CK()- 35,000 IU/L

     5) Myoglobinuria- tubular necrosis & acute renal failure

Diagnosis

    ; muscle biopsy

           - rhabdomyolysis : widely scattered necrosis of m.fibers

    - *between attacks, normal(underlying chronic myopathy없으면)

Prevention

    ; dantrolene sodium before anesthesia

    ; caffeine contracture test

562.3  Glycogenoses - 6 Types

Glycogenosis I (Von Gierke Disease)

     1) not true myopathy

        ; glucose-6-phosphatase deficiency

     2) hypotonic, mildly weak

Glycogenosis II (Pompe Disease)

    ; autosomal recessive

    ; glycolytic lysosomal enzyme acid maltase deficiency

    ; 2 forms

           1) infantile form

             - *severe generalized myopathy, cardiomyopathy

                   - *cardiomegaly & hepatomegaly

             - diffusely hypotonic & weak

             - high elevated serum CK

             - m. biopsy

                           / vacuolar myopathy with abnormal lysosomal enzymatic activity

             - infancy or early childhood 대개 사망

         2) late childhood or adult form

             - *milder myopathy without cardiac or hepatic enlargement

         - not become clinically expressed until later childhood or early adult life

             - high elevated serum CK

    ; Diagnosis

           - m. or liver biopsy tissue에서 quantitative assay of acid maltase activity

Glycogenosis III (Cori-Forbes Disease)

     1) deficiency of debrancher enzyme (amylo-l,6-glucosidase)

     2) the most common glycogenoses

        the least severe clinically

     3) Hypotonia, weakness, hepatomegaly, fasting hypoglycemia

        - 종종 spontaneously resolve

     4) slowly progressive distal m.wasting, hepatic cirrhosis, heart failure

     5) m.biopsy - minor myopathic finding(vacuolation of m.fiber)  

Glycogenosis IV (Andersen disease)

     1) deficiency of brancher enzyme

        ; abnormal glycogen molecule amylopectin liver, RES cell, skeletal &

          cardiac m. 형성

     2) usual sgs

        hypotonia

        generalized weakness

        m.wasting

        contracture 

     3) 4 이전에 hepatic or cardiac failure 대개 사망

        소수에서는 neuromuscular manifestations없는경우도 있음

Glycogenosis V (McArdle disease)

    ; muscle phosphorylase deficiency

    ; AR

  ; Clinical Manifestation

        - *exercise intolerance : cardinal Sx

    - physical exertion -> cramps, weakness, myoglobinuria

    - *serum CK - only during exercise

    - ischemic exercise동안 serum lactate상승없음 (characteristic cl/F)

            <- pyruvate에서 lactate로의 전환 능력없음

    ; Diagnosis

       - muscle biopsy - myophosphorylase deficiency  증명

  ; neonatal form

           - rare

    - feeding difficulties in early infancy,

    - death,

    - slowly progressive weakness         

    ; Prognosis

           - good

Glycogenosis VII (Tarui disease)

     1) muscle phosphofructokinase deficiency

     2) rarer than glycogenosis V

        Cl/M glycogenosis V 유사 - exercise intolerance, clinical course,

                 pyruvate에서 lactate로의 전환능력 결핍

562.4 Mitochondrial Myopathy

# Characteristics

    ; mitochondrial structural, functional abnormalies in muscle, brain, other organs

    ; defects in

           - aerobic cellular metabolism

    - electron transport chain

    - Krebs cycle

    ; *paracrystalline inclusions in EM of muscle biopsy

           - cristae and fusion of cristae

    ; ragged-red muscle fiber

           - *abnormal clumping of oxidative enzymatic activity

Kearns-Sayre Syndrome

  ; Triad

           progressive external ophthalmoplegia

    pigmentary degeneration of retina

    20 이전에 onset

  ; 기타 : heart block, cerebellar deficits, high CSF protein content

  ; abnormal VEP

  ; trunk or extremities weakness or dysphagia 대개 경험하지않는다

    ;  sporadic(most cases)

  ; single large mtDNA deletion

Chronic Progressive External Ophthalmoplegia

    ; limb m.weakness, dysphagia & dysarthria

    ; ophthalmoplegia plus additional CNS involvement

    ; sporadic

           - some autosomal dominant

Myoclonic Epilepsy & Ragged-Red Fibers(MERRF)

MELAS

    ; *Mitochondrial myopathy, Encephalopathy, Lactic acidosis, Stroke-like episodes

    ; Clinical Manifestation

           - stunted growth, episodic vomiting, seizure

           - recurrent cerebral insults

                   / hemiparesis, hemianopia, cortical blindness, dementia

           - 수년내 사망

Leigh's Subacute Necrotizing Encephalopathy

Cerebrohepatorenal(Zellweger) Disease

Cytochrome-C-Oxidase Deficiency

Oculopharyngeal Muscular Dystrophy 

562.5  Lipid Myopathies

 1. muscle carnitine deficiency

     1) autosomal recessive

     2) intestinal mucosa에서 dietary carnitine transport결핍

     3) carnitine from - (1) dietary source

                         (2) lysine & methionine으로부터 liver & kidney에서

                             성됨 

                         (3) m.mitochondria 들어가는 long & medium chain fatty

                             acid carrier

     4) Cl/M - progressive muscular dystrophy

        (1) generalized proximal myopathy

        (2) facial, pharyngeal, cardiac involvement

        (3) late childhood or adolescence sx onset되거나 adult life까지 delay

        (4) slowly progression하나 결국 사망

     5) Dx

        (1) serum CK - mildly

        (2) m.biopsy - m.fiber lipid vacuole

                     - normal or abnormal mitochondria

                     - carnitine in m.biopsy tissue

                        (serum carnitine normal)

     6) Tx 

        (1) special diet - long chain fatty acid낮은 diet

        (2) steroid - fatty acid transport증가

        (3) L-carnitine therapy

        (4) riboflavin

        (5) propranolol

 

 2. Systemic carnitine deficiency

     1) carnitine renal & hepatic synthesis장애

     2) AR

     3) progressive proximal myopathy

        m.biopsy - m.carnitine defi. 유사

     4) 특징

        (1) wweakness onset ; earlier

        (2) endocardial fibroelastosis

        (3) acute hepatic encephalopathy(Reye synd 유사한)

        (4) hypoglycemia

        (5) metabolic acidosis

     5) serum, m., liver carnitine감소

     6) Tx

        ; L-carnitine - blood glucose & serum carnitine level유지시키나

                        ketosis, acidosis, exercise capacity improve에는 not

                        effective

 3. muscle carnitine palmityltransferase(CPT) deficiency

     1) 특징  (1) rhabdomyolysis

              (2) coma

              (3) serum CK

        -- Reye synd 유사

     2) 기타

        (1) exercise intolerance

        (2) myoglobinuria

        -- glycogenosis V & VII유사

     3) fasting hypoglycemia

     4) AR due to defect on chromosome 1 at 1p11-13 locus

562.6  Vitamin E Deficiency Myopathy

 1. antioxidant intake 부족한 경우 myopathy & neuropathy 생김

 2. malabsorption, chronic dialysis, vit E 공급되지않는 premature infant     

     - particularly vulnerable

Chapter 563. Disorders Of Neuromuscular Transmission And Of Motor Neurons

563.1 Myasthenia Gravis

; caused by immunologic neuromuscular blockade

# pathophysiology

    ; *normal acetylcholine (ACh) release

           - but *less responsive postsynaptic muscle membrane or motor end-plate

    ; circulating receptor-binding antibodies

           --> decreased number of ACh receptors

    ; *nonhereditary, autoimmune disorder

# rare familial MG

    ; AR

# infants born to myasthenic mother

    ; transient neonatal myasthenic synd.

    ; secondary to placentally transferred anti-ACh receptor antibodies

Clinical Manifestation

# ★▲early & constant signs

    ; *ptosis

  ; extraocular muscle weakness

# eye Sx

  ; diplopia - older children

  ; hold open eyes with fingers or thumbs if ptosis is severe enough to obstruct vision - young children

    ; *preserved pupillary responses to light

# Dysphagia & facial weakness

# feeding difficulties - often cardinal sign in  early infancy

# Poor head control due to weakness of neck flexors m.

# m. involvement

   (1) bulbar-innervated muscles

   (2) limb-girdle muscles & distal m. of hands; most cases

   (3) fasciculation of muscle, myalgia, and sensory Sx;(-)

   (4) DTR; or rarely lost

# Rapid fatigue of muscles

    ; characteristic feature

   # 다른 neuromuscular diseases와의 DDx

      (1) Ptosis - increases progressively

          (the patient is asked to sustain an upward gaze for 30-90 sec)

      (2) supine position에서 head holding힘듬

      (3) fists repetitive open & close rapid fatigue of hand m.

      (4) fatigue of deltoids 1-2분이상 arms elevation안됨

 if untreated - usually progressive

               - life threatening ; respiratory m.invoIvement & risk of

                                    aspiration

# Familial MG- usually not progressive

# Infants Born To Myasthenic Mother

    (=syndrome of transient neonatal myasthenia gravis)

    ; respiratory insufficiency, inability to suck or swallow, generalized hypotonia & weakness, little spontaneous motor activity for several days to weeks

    ; Some require ventilatory support & feeding by gavage

  ; *abnormal anti-bodies disappear normal strength &  no increased risk for MG later childhood

# hereditary congenital MG

    (1) not related to maternal myasthenia

    (2) often permanent

# abnormality of the acetylcholine receptor channels

    - high conductance & excessively fast closure

    - may be due to a point mutation in a subunit the receptor affecting a

      single amino acid residue

# asso.other diseases

    (1) secondary to hypothyroidism, usually Hashimoto thyroiditis

    (2) collagen vascular diseases(SLE,DM,RA etc)

    (3) Thymomas - not found in children

    (4) oat cell ca. of lung - in adults

Laboratory Finding & Diagnosis

# EMG

    ; *more specifically diagnostic than the muscle biopsy

  ; decremental response to repetitive nerve stimulation

    ; *normal motor nerve conduction velocity

            ; this unique EMG pattern - electrophyslologic correlate of the

             fatigable weakness observed clinically & cholinesterase inhibitor

             투여후에 reversed

            ; myasthenic decrement may be absent

              - in early cases or in pts showing only weakness of EOM

# serum Anti-ACh antibodies

        - not always demonstrated

# Other serologic tests of autoimmune ds

        - ANA, abnormal immune complexes

     4) thyroid profile

     5) serum CK - normal

     6) ECG - normal(heart; not involved)

     7) chest X-ray - enlarged thymus but not thymoma

# muscle biopsy

    ; controversial

        (1) not required in most cases

           17%에서 inflammatory changes (lymphorrhages)

        (2) nonspecific type II muscle fiber atrophy

           (유사하게 나타나는 경우)

           disuse atrophy

           steroid effects on muscle

           polymyalgia rheumatica

           many other conditions

        (3) ultrastructure of motor end-plates

            - simplification of the membrane folds

# Clinical Test For MG

    ; administration of a short-acting cholinesterase inhibitor

         1) edrophonium chloride(Tensilon) (cf.antagonist : atropine)

                 - small test dose IV, initially ;allergic tendency확인위해

           - a few minutes later, full dose of 0.2 mg/kg (max. 10 mg) IV

             30 kg이하에서는 total dose 1-2mg으로 제한해야됨

           - effect> 수초내에 ptosis & ophthalmoplegia improve

                     greatly decreased fatigability of other muscles

              1-2 정도 효과지속

           - young infants에서는 금기 - cardiac arrythmias

        2) neostigmine (IM)

                   - fewer cardiogenic side effects

           - initial test of 0.04mg/kg

           - negative이면 4hr 0.08mg/kg retested

           - maximal effect ; 20-40 min

            muscarinic side effects ; abdominal distention,diarrhea,profuse

                                      tracheal secretions

             => 0.01mg/kg of atropine neostigmine주기전에 투여

Treatment

; some mild MG require no treatment

# Cholinesterase-Inhibiting Drugs

    ; Neostigmine methylsulfate 0.04 mg/kg IM q4-6hr

    ; *oral neostigmine bromide 0.4 mg/kg q4-6hr

    ; If dysphagia is a major problem,식사 30분전에 투여(to improve swalluwing)

    ; Pyridostigmine

           - neostigmine 4 dosage

           - slightly longer acting

    ; overdoses of cholinesterase inhibitors

       - cholinergic crises

    - atropine blocks muscarinic effects, but not block nicotinic effects that produce additional skeletal m.weakness

# long-term steroid treatment (autoimmune basis)

 ; prednisone - often effective

# Thymectomy

 ; ineffective in congenital & familial forms

# Treatment of hypothyroidism

 ; associated MG 좋게함(대개)

# Plasmapheresis

 ; steroid Tx 반응하지않는 경우 특히 유효함

   may provide only temporary remission

# Intravenous immunoglobulin (IVIG)

 ; sometimes beneficial

cf. plasmapheresis & IVIG - most effective in pts with high circulating

       levels of antiACH receptor antibodies

# Neonates with transient maternally transmitted MG

 ; cholinesterase inhibitors 수일 혹은 수주간 투여

   특히 feeding 가능하게하기위해

Complication

     1) neuromuscular blocking drugs(succinylcholine & pancuronium)투여시

        very poor - single dose후에 수주간 paralysis상태로 있을수있음

     2) antibiotics (aminoglycoside; GM etc)

        - MG 악화시킴

Prognosis

; difficult to predict

     1) Some pts - 수개월 또는 수년후 spontaneous remission

     2) others - permanent disease extending into adult life

     3) immunosuppression, thymectomy, and hypothyroidism Tx

               - may provide a cure

Other Causes Of Neuromuscular Blockade

Organophosphate Chemicals(Insecticides)

     ; myasthenia-like synd.

Botuiism

     1) etiology

         ingestion of food containing toxin of Clostridium botulinum

           G(+), spore-bearing, anaerobic bacillus

         Honey - common source of contamination

     2) incubation period ; short, only a few hours

     3) Sx

        (1) nausea, vomiting, & diarrhea 시작

        (2) Cranial nerve involvement

            diplopia

            dysphagia

            weak suck

            facial weakness

            absent gag reflex

            Generalized hypotonia & weakness

            progress to respiratory failure

     4) Tx

        (1) Respiratory support

           ; 수일내지 수주간, toxin 제거될때까지

        (2) Guanidine  35 mg/kg/24 hr

           ; EOM & limb muscle weakness effective

           ; respiratory m. involvement에는 효과없음

        (3) no specific antitoxin

Tick Paralysis

Etiology

        depolarization block하는 neurotoxin에의해서 axonal terminal 부터의

        Ach release장애

        (1) wood tick

        (2) dog tick

        (3) insects in Appalachian and Rocky Mountains of North America

Clinical Manifestation

    ; tick embedded into usually scalp skin

           --> *neurotoxin production is maximal about 5-6 days later

    ; weakness, loss of coordination, ascending paralysis

           - GBS 유사

    ; loss of Tendon reflexes

    ; tingling paresthesia in face & extremities

Diagnosis

        (1) EMG

        (2) nerve conduction studies

        (3) identifying tick

Treatment

    ; must be removed completely - scalp skin 남아있는 head 완전히 없앰

Prognosis

 ; 수시간 혹은 수일내에 회복

563.2 Spinal Muscular Atrophies

; degenerative diseases of motor neurons

    - begins in fetal life & continue to be progressive in infancy & childhood

# classification

  1) SMA type 1 (severe infantile form = Werdnig-Hoffmann disease)

  2) SMA type 2 (late infantile and more slowly progressive form)

  3) SMA type 3 (more chronic or juvenile form = Kugelberg-Welander disease)

  4) Fazio-Londe disease

     ; variant of SMA

     ; progressive bulbar palsy

     ; spinal cord보다는 brain stem내에서 motor-neuron degeneration있음

Etiology

; pathologic continuation of process of programmed cell death that is normal in embryonic life

Clinical Manifestation

SMA Type 1 (Severe Infantile Form = Werdnig-Hoffmann Disease)

    ; Cardinal Features

           - *Severe hypotonia, generalized weakness, thin muscle mass, absent tendon stretch reflexes, involvement of tongue, face & jaw muscles, sparing of EOM & sphincters

    ; 출생시부터 symptomatic - respiratory distress & unable to feed가능

    ; Congenital contractures

         - 10% of severely involved neonates

    ; gravity 이길수 없고 거의 움직이지 않으며 head control안됨

    ; 2세경 2/3에서 사망

SMA Type 2 (Late Infantile And More Slowly Progressive Form)

   (1) early infancy - usually, sucking, swalloing, and respiration가능

   (2) progressive weakness

   (3) Nasal speech & problems with deglutition develop later

   (4) Scoliosis - major complication in many pts with long survival

SMA Type 3 (More Chronic Or Juvenile Form = Kugelberg-Welander Disease)

   (1) mildest SMA

   (2) normal in infancy

   (3) progressive weakness - proximal(particularly, shoulder girdle m.)

                           - ambulation가능

   (4) bulbar muscle weakness - rare

   (5) middle adult life까지 생존가능

Other Manifestations

    ; Fasciculations

           - specific clinical sign of denervation of muscle

    - continuous involuntary wormlike movements

      deltoid

       biceps brachii

      quadriceps femoris

      tongue - best observed

  ; *tremor due to fasciculation & weakness in outstretched finger

  ; *no myalgia

  ; *no heart involvement

  ; *normal intelligence, appear brighter

Laboratory Finding

  ; serum CK

           - may be normal

    - *more commonly is mildly elevated

    ; normal motor nerve conduction studies

       - peripheral neuropathy와의 DDx 중요한 feature

  ; EMG

           - fibrillation potentials & signs of denervation of muscles

Diagnosis

     1) muscle biopsy

        ; characteristic pattern of perinatal denervation

        (1) Groups of giant type I fibers fascicles of severely atrophic

            fibers mix

        (2) In juvenile SMA ; similar to adult muscle

     2) Sural nerve biopsy

        ; sometimes, mild sensory neuropathic changes

         & slowed sensory nerve conduction velocity 가능

     3) autopsy findings

        (1) mild degenerative changes in+-sensory neurons of dorsal root ganglia

                                        +-somatosensory nuclei of thalamus

            ; not perceived clinically as sensory loss or paresthesias

        (2) most pronounced neuropathologic lesions

            ; extensive neuronal degeneration and gliosis

              in ventral horns of spinal cord

                 brain stem motor nuclei(특히 hypoglossal nucleus)

Genetics

     (1) autosomal recessive (most cases) (AD 가능)

     (2) incidence - 1:25,000

     (3) 두번째로 흔한 neuromuscular ds.

          cf) 1st - Duchenne muscular dystrophy

     (4) defective gene - chromosome 5 at the 5q11-13 locus

Treatment

     (1) no medical treatment to delay the progression

     (2) Supportive therapy

         ; orthopedic care(특히 attention to scoliosis and joint contractures)

          mild physiotherapy

          mechanical aids(assisting to eat & to be as functionally

             independent as possible)

Other Motor Neuron Diseases

Poliomyelitis

     2) Coxsackie & ECHO viruses, or the live polio vaccine virus

        ; polio 유사하나 대개 milder

     3) Dx ; Serologic tests for specific antibodies and viral cultures of CSF

Juvenile Form Of Amyotrophic Lateral Sclerosis

- rare

     1) Upper & lower motor neuron loss ; evident clinically, unlike SMA

     2) progressive course & fatal

Pena-Shokeir & Marden-Walker Syndromes

     1) progressive motor neuron degenerations

     2) severe arthrogryposis

     3) congenital anomalies of many organ systems

Metabolic Diseases Of Nervous System

     1) gangliosidosis (Tay-Sachs disease)

     2) ceroid-lipofuscinosis (Batten disease)

     3) glycogenosis II (Pompe disease)

Chapter 564. Hereditary Motor-Sensory Neuropathies

 - a group of progressive diseases of peripheral nerves

 - Motor components clinical picture dominant하나 후에 sensory & autonomic

   involvement expressed

564.1 Peroneal Muscular Atrophy

(Charcot-Marie-Tooth Disease; HMSN Type I)

Genetics

     1) the most common genetically determined neuropathy

     2) prevalence - 3.8: 100,000

     3) autosomal dominant(83%) - abnormal gene; 17p11.2 locus

        X-linked - much rarer , defect at the Xq13.1 locus(causing mutations in

                                the gap junction protein connexin-32)

Clinical Manifestation

     1) Sx onset

        (1) late childhood or early adolescence까지 대개 asx하나 young chilldren

            에서 때때로 2세경 gait disturbance sg보일수 있음

        (2) peroneal & tibial nerves - earliest & most severely affected

        (3) 환아는 흔히 - clumsy(서투른), falling easily, 자기발에 걸려 넘어짐

        (4) Sx onset 40대까지 delay될수 있음

     2) 양상

        (1) Muscles of ant. compartment of lower legs wasting

            - legs ; characteristic "storklike" contour

        (2) muscular atrophy

            - Progressive weakness of dorsiflexion of ankle

            - eventual foot drop

        (3) process - bilateral but may be slightly asymmetric

        (4) pes cavus deformities - because of denervation of intrinsic foot

                                    muscles, further destabilizing the gait

        (5) advanced cases - contractures of wrists & fingers

                              "claw hand"

        (6) proximal muscle weakness - late manifestation & usually mild

        (7) Axial muscles - not involved

        (8) slowly progressive throughout life

            but,드물게는 년에 걸쳐 accelerated deterioration of function

        (9) Most pts - ambulatory & normal longevity

       (10) Sensory involvement

           proprioceptive information & vibratory sense담당하는 large

              myelinated fiber involve

           pain & temperature threshold  상승

           tingling or burning sensations of feet

           pain - rare

       (11) muscle mass감소 - nerves trauma or compression에대해 more

                              vulnerable

       (12) Autonomic manifestations

           poor vasomotor control

           blotching or pallor of skin of feet

           inappropriately cold feet

       (13) palpably enlarged nerves

       (14) Tendon stretch reflexes - lost distally

       (15) Cranial nerves - not clinically affected

       (16) Sphincter control - well preserved

       (17) Autonomic neuropathy - heart, GI tract, or bladder에는 not affected

       (18) Intelligence - normal

     3) Davidenkow syndrome - variant of HMSN type I with a scapuloperoneal

                              distribution

 3. Lab/F

     1) Motor & sensory nerve conduction velocities - greatly reduced

        ;때로는 normal conduction time 20%까지 느려짐

     2) EMG & muscle biopsy - not usually required

        ; evidence of many cycles of denervation & reinnervation

     3) Serum CK - normal

     4) CSF protein may be elevated(but no cells in CSF)

     5) sural nerve biopsy

        ;특히 family Hx없을때 diagnostic

        (1) reduced large & medium sized myelinated fibers

        (2) increased collagen

        (3) characteristic"onion-bulb formations"

            - axon주위로 Schwann cell cytoplasm proliferation

              ; interstitial hypertrophic neuropathy

        (4) Extensive segmental demyelination and remyelination

 

 4. Tx

     1) Stabilization of ankle - primary concern

     2) In early stages

        (1) stiff boots - extend to midcalf often suffice

            특히 빙판,눈길, 같은 uneven surfaces위를 걸을때

        (2) weakened dorsiflexors of ankle - lightweight plastic splints

        (3) external short leg braces - complete foot drop 필요

        (4) Surgical fusion of ankle

        (5) leg - should be protected from traumatic injury

        (6) Compression neuropathy during sleep - may be prevented by soft

            pillows beneath or between lower legs in advanced cases

        (7) phenytoin or carbamazepine       

            - burning paresthesias of feet

     3) arrest or slow the progression시킬수 있는 medical Tx 없음

564.2  Peroneal Muscular Atrophy,Axonal Type(Hmsn Type Ii)

 1) clinically similar to HMSN typeI

    but slower progression & less disability

 2) EMG ; denervation of muscle

 3) Sural nerve biopsy ; axonal degeneration

 4) locus ; chromosome 1 at 1p35-36

    autosomal dominant

564.3  Dejerine-Sottas Disease (HMSN Type III)

 1) interstitial hypertrophic neuropathy of autosomal dominant transmission

 2) HMSN typeI 유사하나 more severe

 3) early infancy sx onset & rapidly progressive

 4) Pupillary abnormalities - (1) lack of reaction to light

                              (2) Argyll-Robertson pupil

 5) Kyphoscoliosis & pes cavus deformities(35%)

 6) Nerves ; palpably enlarged at early age

 7) sural nerve biopsy ; more pronounced onion-bulb formations & Hypomyelination

 8) genetic locus of 17p11.2 (identical to that of HMSN type I)

 9) autosomal recessive form of Dejerine-Sottas disease ; controversial

564.4  Roussy-Levy Syndrome

 ; HMSN typeI + Friedreich ataxia

564.5  Refsum Disease

 1) Etiology

    ; phytanic acid pristanic acid 되는 α-oxidation 대한 enzymatic block

      - Phytanic acid plasma, CSF & brain tissue greatly elevated

        cf) Phytanic acid : branched-chain fatty acid derived mainly from

                            dietary sources(spinach,nuts,coffee)

 2) CSF ; albuminocytologic dissociation

          (protein conc.- 100-600mg/dl)

 3) Cl/M

    4-7세경 대개 onset

    intermittent motor & sensory neuropathy

    Ataxia

    progressive neurosensory hearing loss

    retinitis pigmentosa & loss night vision

    ichthyosis

    liver dysfunction

 4) Dx

    delayed motor & sensory nerve conduction velocities

 5) Tx

    dietary management & periodic plasma exchange

564.6  Giant Axonal Neuropathy

 1) 특징 ; autosomal recessive

           early childhood onset

           progressive mixed peripheral neuropathy

 2) Cl/M

    Ataxia & nystagmus

    peculiar curly reddish hair

    Focal axonal enlargements in both PNS & CNS

    intact myelin sheath

 3) disorder of neurofilament synthesis or organization

564.7  Congenital Hypomyelinating Neuropathy

(신판추가)

 1) motor and sensory peripheral nerves normal myelination결핍

    (but not of CNS white matter)

    ; not a degeneration or loss of previously formed myelin

      -> leukodystrophy DDx

 2) preserved Schwann cells & normal axons

 3) suggest autosomal recessive

 4) Cl/M

    ; 출생시 부터 sx존재

    hypotonia & developmental delay - hallmark clinical findings

    Cranial nerves - inconsistently involved

    respiratory distress & dysphagia - rare complications

    Tendon reflexes - absent

    Arthrogryposis - at birth( 50%)

 5) Dx

    slow motor & sensory nerve conduction velocities

    sural nerve biopsy (confirmed)

       ; lack of myelination of large and small fibers

         sometimes interstitial hypertrophic reactive changes

    Muscle biopsy ; mild neurogenic atrophy

    No inflammation in muscle or nerve

564.8  Leukodystrophies

  CNS white matter degenerative diseases peripheral neuropathy야기

   ; Krabbe's disease (globoid cell leukodystrophy)

     metachromatic leukodystrophy

Chapter 565. Toxic Neuropathies       

 

 1. Heavy metals

     1) lead poisoning

        ; especially if chronic, mainly motor neuropathy(selective large nerves)

          common peroneal n.

          radial

          median n.

        - mononeuritis multiplex

      2) Arsenic

         ; painful burning paresthesia    

           motor polyneuropathy

 2. Antimetabolic drugs

     ; vincristine - polyneuropathies

 3. Chronic uremia

     ; toxic neuropathy & myopathy

     - due to excessive levels of circulating parathormone

     -> Reduction in serum parathyroid hormone -- clinical improvement & return

        to normal of nerve conduction velocity

Chapter 566. Autonomic Neuropathies

566.1 Familial Dysautonomia (=Riley-Day Syndrome)

autosomal recessive

Eastern European Jewsis - common

incidence - 1:10,000-20,000

carrier state - 1%

*defective gene - 9q31-33 locus

Pathology

reduced number of small unmyelinated nerve fibers

    ; carry pain,temperature,& taste sensation

    ; mediate autonomic functions

deficient large myelinated afferent nerve fibers & Golgi tendon organs

absent or reduced in number of Fungiform papillae of the tongue (taste buds)

Clinical Manifestation

) infancy   poor sucking and swallowing

            Aspiration pneumonia

) childhood Feeding difficulties - major symptom

            Vomiting crises

            Excessive sweating & blotchy erythema of skin

               - 특히 mealtime or excited

            Breath-holding spells & syncope

               - 5 년내에 Common

3) older children

            insensitivity to pain - frequent traumatic injuries

            Corneal ulcerations

            tongue ulceration due to newly erupting teeth

            delayed,clumsy,ataxic Walking -poor sensory feedback from

                                              m. spindles

             Tendon stretch reflexes(-)

 4) Scoliosis - serious complication (usually if progressive)

 5) 생후 2-3개월에 정상적으로 있어야 Overflow tearing with crying

    없음 ; 시기후에도 없거나 심각하게 감소됨

 6) generalized major motor seizures

    40%

    대개 no precipitating event

       breath-holding, extreme fevers동안 acute hypoxia동반되는 경우도

       있음

    usually impaired intellectual function

    epilepsy와는 무관

 7) Puberty - often delayed(특히 in girls)

 8) Body temperature - poorly controlled (hypothermia & extreme fevers)

 9) Speech - often slurred or nasal

# autonomic crises

  ; *3세이후

  ; *대개 24-72시간 or 수일간 지속되는 attacks of cyclic vomiting

  ; Retching & vomiting 15-20분마다 다음과 관련되어 나타남

   hypertension

   profuse sweating

   blotching of skin

   apprehension

   irritability

  ; prominent gastric distention

           --> abdominal pain & respiratory distress

    ; Hematemes due to pernicious vomiting

Laboratory Finding

# ECG - Prolonged correcting QT intervals with lack of appropriate

         shortening with exercise ; aberration in autonomic regulation of

                                    cardiac conduction

# Chest X-ray

   (1) atelectasis

   (2) pulmonary changes resembling cystic fibrosis

# *Urinary vanillyl-mandelic acid(VMA) & homovanillic acid (HVA)

# Plasma dopamine-β-hydroxylase(converts dopamine to epinephrine)

# sural n.biopsy - unmyelinated fibers 감소

Diagnosis

# slow IV infusion of norepinephrine

  --> exaggerated pressor response

# infusion of methacholine

  --> increased hpotensive response

# *1:10,000 histamine phosphate, Intradermal injection

    --> *no normal axon flare, local pain (-) or

# *instillation of 2.5% methacholine into the conjunctival sac

  --> miosis in patients with familial dysautonomia

        ; nonspecific sg of parasympathetic denervation from any cause

           ; only one eye in this test, with the other eye as a control at 5min inverval for 20min

Treatment

# Symptomatic Tx

  1) special attention to the respiratory & GI systems

  2) methylcellulose eye drops or topical ocular lubricants

     ; prevent corneal ulceration

  3) orthopedic management of scoliosis and joint problems

  4) appropriate anticonvulsants for epilepsy

# Chlorpromazine

 (1) effective antiemetic

 (2) may be given as rectal suppositories during autonomic crises

 (3) reduces apprehension and lowers BP

Dehydration and electrolyte disturbances 교정

Bethanechol

 ; alternative drug for cyclic vomiting

   useful for enuresis, augment tear production

protection from injury(<- lack of pain)

scoliosis ; surgical Tx할수도

Prognosis

     1) poor

     2) 대개 childhood 사망 - chronic pulmonary failure or aspiration

566.2  Other Autonomic Neuropathies

Myenteric Plexus Neuropathies

     1) Aganglionic megacolon (Hirschsprung disease)

        (1) colon & rectum segment  submucosal & myenteric plexuses내에있는

            parasympathetic neurons embryonic development failure 

        (2) gut wall smooth muscle longitudinal and circular layers사이에

            있는 nerves hypertrophic해짐

        (3) absent ganglion cells

Congenital Insensitivity To Pain And Anhldrosis

    1) uncertain genetic transmission

        boys>>girls

     2) early infancy 나타남

     3) Sx ; 1. warm environmental temperature high fever (;발한×)

             2. frequent burns & traumatic injuries (;pain perception(-))

     4) normal intelligence

     5) Nerve biopsy

        ; impulses of pain, temperature, & autonomic functions 전달하는

          unmyelinated nerve fibers almost total absence

Reflex Sympathetic Dystrophy

(신판추가)

     1) local causalgia - a hand or foot(usually)

     2) affected zone에서 vasomotor instability와함께 burning pain &

         hyperesthesia동반

     3) chronic state - (1) atrophy of skin appendages

                        (2) cool & clammy skin

                        (3) disuse atrophy of underlying muscle and bone

     4) 드물게 one extremity이상 involved하기도

     5) no objective signs of arthritis

        pain - movement 연관되어 ↓↑; immobilization provides some relief

     6) The most common preceding event

        - local trauma

          ; 수일 or 수주전에 contusion, laceration, sprain, or fracture

     7) pathogenesis

        ; reflexive overactivity of autonomic nerves in response to injury

     8) Tx

        (1) regional sympathetic blockade temporary relief제공

        (2) physiotherapy ; helpful

        (3) 수주 or 수개월후 spontaneously resolve(somecases)

            but others continue to be Sx & require sympathectomy

     9) in some cases, strong psychogenic component is suspected(입증은 안됨)

CHAP 567. Guillain-Barr Syndrome

; postinfectious polyneuropthy

; 주로 motor demyelination,but sensory n. involve

; affects all ages

; not hereditary

Clinical Manifestation

1. paralysis

    ; usually follow nonspecific viral infection by 10 days

           - GI (Campylobacter sp.) or URI symptoms

    ; begins lower extremities

           --> ascending involvement

           --> finally bulbar involvement

           *(= Landry's ascending paralysis)

    ; relatively symmetrically (asymmetry , 9% )

    ; gradual onset

           --> progress over days or weeks

           *cf. when abrupt onset

                   : tenderness to palpation & pain in muscles in initial stages

2. irritable

3. inability or refusal to walk(=flaccid tetraplegia)

4. paresthesias(some cases)

5. Bulbar involvement

  ; 50%

  ; Respiratory insufficiency

         - dysphagia & facial weaknes : often impending signs of respiratory failure

  ; difficulty in eating

           --> risk of aspiration

  ; EOM involvement - rare

       - uncommon variant : severe oculomotor & other cranial neuropathies in early course

           *- Miller-Fisher syndrome : acute external ophthalmoplegia, ataxia & areflexia

    ; Papilledema

6. Urinary incontinence or retention of urine

  ; about 20% ,but usually transient

7. Tendon reflexes(-)

  ; usually early

    ; sometimes preserve until later

8. autonomic nervous system involvement

    ; lability of BP & HR

  ; postural hypotension

  ; profound bradycardia

    ; asystole

# Clinical Course

    ; usually benign

           - spontaneous recovery within 2~3 wk

    ; most regain full m. strength

           - some residual weakness

    ; recovery

           - inverse to direction of involvement

           - recovery of bulbar function first, lower extremity weakness resolving last

           - tendon reflexes : usually the last function to recover

# Asso. with Mycoplasma pneumoniae, Campylobacter spp.

# chronic forms of Guillain-Barre syndrome

    ; 간간이 재발하거나 수개월에서 수년간 improve없는경우

  ; chronic relapsing polyradiculoneuropathy & chronic unremitting polyradiculoneuropathy

relapse rate : 7%

Laboratory finding and Diagnosis

1. CSF study ; essential for Dx

  ; elevated CSF protein

           - 정상상한치의 2배이상

           - 2~5주사이 maximum

           - glucose - normal

    - no pleocytosis(WBC 10개미만)

    - bacterial cultures(-)

       - viral cultures - rarely isolate specific viruses

2. NCV

    ; motor nerve conduction velocities

        - greatly reduced

    ; sensory nerve conduction time

           - often slow

3. EMG

  ; evidence of acute denervation of muscle

4. Serum CK ; mildly elevated or normal

5. Muscle biopsy ; not usually required for Dx

    - normal in early stages

           - denervation atrophy in chronic stages

6. Sural nerve biopsy ; usually not required for Dx

       - segmental demyelination

    - focal inflammation

       - wallerian degeneration

Treatment

1. *hospital for observation in early stages of this acute disease

    ; *possible rapidly involvement respiratory muscle during the next 24 hr

2. when rapidly progressive ascending paralysis

    ; *plasma exchange therapy - effective

    ; steroids

    ; immunosuppressive drugs

3. Intravenous immunoglobulin (IVIG) ; alternative & widely used in many autoimmune disorders

4. Supportive care

    ; respiratory support

    ; prevention of decubitus in children with flaccid tetraplegia

    ; secondary bacterial infections Tx

5. Chronic relapsing polyradiculoneuropathy or unremitting chronic neuropathy

    ; plasma exchange - sometimes requiring as many as 10 exchanges daily

  ; IVIG

    ; Steroid & immunosuppressive drugs - less predictable

    ; High-dose 'pulsed' methylprednisolone IV - successful in some cases

Prognosis

; chronic forms - major residual handicaps

Chapter 568. Bell's Palsy

# 특징

    1) acute unilateral facial nerve palsy

     - 다른 cranial neuropathies brain stem dysfunction과는 무관

  2) common disorder at all ages from infancy through adolescence

  3) systemic viral infection 대개 2주경에 abrupt onset

     ; preceding infection

       (1) Epstein-Barr virus(20%)

       (2) Lyme disease

       (3) herpesvirus

       (4) mumps virus

  4) active viral invasion이라기보다는 postinfectious allergic or immune

     demyelinating facial neuritis 생각됨

  5) hypertension 동반

Clinical Manifestation

# facial manifestations

    ; paretic upper & lower face

  ; drooped corner of mouth

  ; unable to close the eye on the involved side

        --> exposure keratitis at night

# loss of Taste

    ; *50%, ant. 2/3 of tongue

# Numbness & paresthesias (-)

Treatment

     1) methylcellulose eye drops or ocular lubricant

        ; cornea보호 ,특히 at night

     2) Steroids

        ; not induce remission & not recommended

     3) Surgical decompression of the facial canal

        ;이론상, swollen facial nerve에대한 more space제공

          not proved to be of value

Prognosis

; excellent

1)  85%이상 - spontaneous recovery with no residual facial weakness

    10% - mild facial weakness남김

    only 5% - permanent severe facial weakness

2) chronic cases(수주내에 recover안되는)

   - electrophysiologic examination of facial n. 필요

     ;to determine the degree of neuropathy & regeneration

   - 다음의 질환들을 고려

      1. facial nerve tumors : schwannomas, neurofibromas

      2. infiltration of facial nerve by leukemic cells

                                   or by a rhabdomyosarcoma of middle ear

      3. brain stem infarcts or tumors

      4. traumatic injury of facial nerve

Facial Palsy At Birth

1) 대개 delivery동안 forceps application에의한 compression neuropathy

   - 수일에서 수주내에 대부분 spontaneous recovery

2) Congenital Bell's palsy - 진단될수 없음

3) Congenital absence of depressor angularis oris muscle

   - facial asymmetry초래(특히 울때)

   - facial nerve lesion아님

   - cosmetic defect

   - feeding장애없음